The basic objective of this research program is to develop specific information about the molecular basis for the mutagenicity of cyclopenta(c,d)pyrene (CPP), a polycyclic aromatic hydrocarbon (PAH) . We propose to study the structure-reactivity relationships of CPP, its mutagenically active metabolities, and mutagenically active synthetic derivatives of CPP which are analogs of active metabolites. We will also determine the identity of specific CPP-DNA adducts and will attempt to define the roles of DNA repair pathways in the conversion of these adducts to specific mutations. The CPP metabolites will be separated and identified, and the mutagenically active metabolites, which are expected to be arene-oxides, will be synthesized. Analogs of the arene-oxides, such as alpha-haloalkylpyrenes, will also be synthesized and tested for mutagenicity. CPP-DNA adducts will be isolated from both in vitro and in vivo exposures of DNA to directly mutagenic CPP derivatives and adduct structures will be determined. Bacterial mutants with genetically defined defects in DNA recombination and repair functions will be exposed to mutagenic CPP derivatives and the rate and extend of repair of CPP induced DNA damage will be determined. Measurement of CPP induced mutagenesis and killing, in conjunction with the biochemcal measurements of repair activity, will permit the definition of roles for both specific CPP-DNA adducts and repair pathways in mutation induction.